Ammonia → 4-(1-Nitro-isoquinoline-5-sulfonyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 251803Notes

Reaction equation

HRID 251803 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([S:15]([C:18]2[C:19]3[CH:20]=[CH:21][N:22]=[CH:23][C:24]=3[CH:25]=[CH:26][CH:27]=2)(=[O:17])=[O:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:28]([O-:30])=[O:29].[Na+].C(OC(=O)C)(=O)C.N>CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([S:15]([C:18]2[C:19]3[CH:20]=[CH:21][N:22]=[C:23]([N+:28]([O-:30])=[O:29])[C:24]=3[CH:25]=[CH:26][CH:27]=2)(=[O:17])=[O:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 7918Acetic Anhydride2×HCID 23668193Sodium Nitrite2×HCID 66868231Tert-butyl 4-(isoquinolin-5-ylsulfonyl)-1,4-diazepane-1-carboxylate

Product 1

HCID 668684924-(1-Nitro-isoquinoline-5-sulfonyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent3×

Procedure

To a stirred solution of the isoquinoline from step A (1.17 g, 3.0 mmol) in anhydrous DMSO (12 mL) was added sodium nitrite (1.24 g, 18 mmol). To the mixture was added slowly over 30 min a solution of acetic anhydride (1.84 g, 18 mmol) in anhydrous DMSO (12 mL). The mixture was stirred overnight and TLC showed most starting material remained. More sodium nitrite (1.24 g, 18 mmol) and acetic anhydride (1.84 g, 18 mmol) in anhydrous DMSO (12 mL) was added and stirring was continued for about 1 h. During this period yellow solid precipitated and TLC showed a new product at Rf 0.5 (hexane/EtOAc 1:1). The mixture was poured into a saturated aqueous solution of sodium bicarbonate (100 mL) and extracted with EtOAc (100 mL×2). Chromatography on silica eluting with 20% EtOAc/Hexane gave an oil. (0.81 g, 62%). LCMS (+APCI) m/z 454 (M+H+NH3).

Workup

  1. stirringstirring
  2. waitwas continued for about 1 h
  3. customDuring this period yellow solid precipitated
  4. additionThe mixture was poured into a saturated aqueous solution of sodium bicarbonate (100 mL)
  5. extractionextracted with EtOAc (100 mL×2)
  6. customChromatography on silica eluting with 20% EtOAc/Hexane gave an oil

Sources & evidence

ORD record
ord-9dfcee990f2f4b6793ee57e9b72c3dd7
Source dataset
uspto-grants-2011_01
Patent number
US07867999B1

Reaction notes

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